Method and apparatus for treatment of viral diseases

ABSTRACT

An apparatus and method for treating viral infections delivers electrical stimulation to the skin or mucosa of a patient. The electrical stimulation is applied as a series of electrical pulses having different electrical characteristics. The apparatus may include a housing having at least two electrodes supplied with both AC and DC voltage, and powered by a battery. The electrodes are designed so as to maximize contact with the patient.

RELATED APPLICATIONS

[0001] This is a continuation application of copending application Ser.No. 09/727,287 entitled METHOD AND APPARATUS FOR TREATMENT OF VIRALDISEASES filed on Nov. 29, 2000, which application is herebyincorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The invention relates to a method and apparatus for deliveringelectrical stimulation to pathological tissue, and more particularly, totreating viral infections by applying a series of electrical pulseshaving different maximum amplitudes to the affected skin or mucosa.

[0004] 2. Description of the Related Art

[0005] Viruses are the smallest infectious agents and contain a moleculeof nucleic acid (RNA or DNA) as their genome. Nucleic acid is enclosedin a protein shell. The viral nucleic acid contains informationnecessary for programming the infected host cell to synthesize thespecific number of macromolecules. Toward the end of the replicativecycle, more viral nucleic acids and coat proteins are produced. The coatproteins assemble together to form the symmetrical protein shell whichencloses the nucleic acid genome.

[0006] There are eight identified herpes viruses that have beenassociated with human disease conditions. The alpha-herpes viruses,HSV-1, HSV-2, and VZV-2, known as oral herpes, genital herpes, andherpes zoster respectively, are neurotropic since they actively infectnervous tissue. Five other herpes viruses are lymphotropic since theyreplicate in the lymphatic system. These include HCMV (humancytomegalovirus), HHV-6, HHV-7, HHV-8 (KHSV) and EBV. HHV-6 has beenassociated with multiple sclerosis. HHV-8 (KHSV) and EBV have beenlinked to the human cancers Kaposi's sarcoma and Epstein-Barr disease.

[0007] Disease states are also caused by a variety of other viruses.Viral hepatitus is a serious liver disease of particular concern forhealthcare professionals. One form of hepatitus, hepatitus C, isconsidered responsible for approximately 10,000 deaths per year. Thehuman papilomavirus (HPV) is responsible for most of the cervicalcancers worldwide, genital warts and the formation of verrucae, wartsthat form on the soles of the feet. HPV has also been associated withseveral oral cancers. In addition, the HIV virus has killed more than 19million people and infected 34 million more, causing an epidemic thatwill continue to devastate communities around the world.

Oral Herpes: The HSV-1 Virus

[0008] Herpes simplex virus (HSV) infections of the oral tissues areamong the most common infectious illnesses involving man. Both primary(initial) and recurrent forms of the infection occur, these beingreferred to as acute primary herpetic gingivo stomatitis, and recurrentherpes labialis. Although oral herpes infections may be consideredprimarily nuisance diseases, gingivostomatitis can be a very painful anddebilitating illness, while recurrent oral herpes in immunosuppressedsubjects may be severe and even life-threatening (Overall, 1979; Ho,1979; Faden et al, 1977).

[0009] The vast majority of oral herpes infections are caused by the HSVtype 1 strain. There are no precise data for the frequency of oralherpes infections. It is estimated that there are about 500,000 cases ofherpes stomatitis each year in the U.S. Recurrent herpes labialis occursin approximately one-third of the population and the mean number ofepisodes per year in individuals with recurrent disease is 1.6 (Overall,1979). This projects at about 100 million episodes of herpes labialis inthe U.S. each year.

[0010] There are several factors that contribute to the significance oforal herpes infections. First, herpes gingivostomatitis can be a severeillness. Fever, toxicity, and exquisitely painful mouth lesions mayinterfere with fluid intake and require hospitalization for intravenousfluids. Second, frequent recurrent lesions of the lips are of cosmeticconcern, particularly in females. Third, cold sores may be the source ofHSV for transmission to immunosuppressed or other hospitalized patients.Fourth, oral herpes in the immunosuppressed patient is often a severe,life-threatening disease. Finally, there is currently no satisfactoryand effective form of therapy for either primary or recurrentmucocutaneous HSV disease in the normal host.

[0011] Most patients develop vesicles within 12 hours, which rupture toform ulcers or crusts in 36 to 48 hours. Most patients lose the crustand have healed ulcers by day 8 to 10. Results from clinical trials onrecurrent herpes labialis has shown that about 25% of patients hadepisodes one or more times a month, almost two-thirds had one episodeevery 2-4 months, and less than 25% had an episode less often than every4 months (Spraunce et al, 1977).

Genital Herpes: The HSV-2 Virus

[0012] Despite the emphasis and publicity on safe sex to prevent AIDS, arecent study by the Centers for Disease Control has shown that genitalherpes has increased fivefold among white teenagers since the late1970's, and doubled among whites in their 20's (New Eng. J ofMedicine,Oct. 16, 1997). One in five Americans over the age of 12 yearscarries the virus that causes genital herpes, with 500,000 new casesoccurring each year.

[0013] It is currently standard practice in the U.S. to perform Cesareandelivery on pregnant women with recurrent herpes to reduce the risk oftransmission of the virus to newborns (J. Obstetrics & Gynecology,October 1996). In spite of this, 20-30% of all infants born via Cesareandelivery still have the herpes virus. More than 40% of newborns infectedwith HSV die or suffer neurologic impairment. What exacerbates thisproblem is that women are 45% more likely to be infected with HSV-2 thanmen. Since there has been a dramatic increase in genital herpes amongthe younger generations, it means that a substantial number of womenentering their childbearing years are infected with HSV-2, or are atrisk of contracting infection. Despite antiviral therapy, neonatalherpes is still a major life threatening infection.

[0014] After inoculation and limited replication at genital sites, HSV-2ascends along neuronal axons to establish latent infection in thelumbosacral ganglia. During this initial phase, infectious virus ispresent at genital sites for days or weeks, usually without lesions.When a new cycle of viral replication is triggered, reactivation occursand infectious virus is delivered back down the neural pathways to themucosa or skin. The return of infectious virus to genital sites duringHSV-2 reactivation rarely causes any symptoms. HSV-2 is a chronic,persistent infection that causes subclinical reaction in about 1% ofinfected persons. Since about 45-50 million people in the U.S. areinfected, HSV-2 can spread efficiently and silently through thepopulation. People who have sexual contact with many partners willfrequently have exposure to an infected person who is shedding HSV-2. Asthe overall prevalence of HSV-2 infection continues to rise, contactwith fewer partners will permit exposure.

[0015] The concept that HSV persists in the nuclei of cells in thesensory ganglia suggests that any topical treatment will be ineffectivein destroying the virus in these hidden locations. About 25 viruses havebeen placed in the HSV group and they all contain a core of doublestranded DNA surrounded by a protein coat that exhibits isocahedrilsymmetry. This in turn is enclosed in an envelope which containsessential lipids. The structural proteins of herpes simplex virusinclude nine polypeptides which have been found in the enveloped virion,two polypeptides which are associated with the envelope, two argininepolypeptides within the virus core, as well as guanine and cytosine. Thevirus enters the cell either by fusion with the cell membrane or bypinocytosis. It is then uncoated and the DNA becomes associated with thenucleus. Soon after infection the virus codes for its own DNA polymeraseand other enzymes such as thymidine kinase which is associated with theDNA replication.

[0016] A variety of treatments have been used for genital herpes butnone is entirely satisfactory. No satisfactory vaccine has been found.In superficial infections, topical agents such as Idoxuridine,Triflurothymidine, or Acyclovir are sometimes effective. The drug ofchoice for the treatment of herpes simplex is Acyclovir which is theonly FDA approved drug. Sales of Zovirax® (Burroughs Wellcome) weregiven at about $500M. Annual estimated sales for this product exceeded$2 billion worldwide in 1997. Administered orally for systemicabsorption, Acyclovir is limited by several factors:

[0017] 1) side effects include rash, nausea, vomiting, diarrhea, orpain, burning or itching at the site where the drug is applied, anorexiaand possible eye injures.

[0018] 2) cost; the average annual cost to a patient is around $1000.

[0019] 3) emergence of drug-resistant virus strains.

[0020] 4) presence of a large number of “early reactivation” patientsfor whom Acyclovir does not work.

[0021] 5) a 6-10 day treatment cycle; patients with HSV-1 (oralherpes/cold sores) must decide if treatment is worth 6-10 days use of anexpensive systemic drug with potential side effects.

[0022] First episodes of the virus should all be treated as early aspossible with one of three available oral antiviral agents. Effectivetreatments include: Acyclovir (Zovirax™) where the usual dose is 200 mgfive times daily. Valacyclovir HCl (Valtrex™) is an improved oralformulation of Acyclovir which requires less frequent dosing at 500 mgtwice daily. Famciclovir (Famvir™) is the oral formulation ofpenciclovir and it is dosed for primary infections at 250 mg three timesdaily. Studies have proven all three drugs to be equally effective. InNorth America, first episode treatment is generally prescribed for 10days, but in Europe and the UK, treatment is generally prescribed for 5days. These antiviral medications can be taken orally very early in arecurrent episode.

Herpes Zoster

[0023] Herpes zoster, also known as shingles, is due to invasion ofposterior root ganglia by the causative virus and is characterized bysevere pain followed by a rash over cutaneous distribution of theaffected nerve. The virus, varicella-zoster (VZ), causes two diseases,varicella (chickenpox) resulting from the first exposure to the virus inchildhood, and zoster, a secondary infection due to reactivation of thelatent VZ virus. Shingles is a painful and potentially debilitatingdisease that affects 750,000 people each year in the U.S. The conditionis most commonly experienced by older Americans and is caused by areactivation of the varicella-zoster virus, the same herpes virus whichcauses chickenpox. A major challenge for physicians in managing patientswith shingles is alleviating the severe pain associated with an activeshingles rash, as well as postherpetic neuralgia (long-term debilitatingpain) which may occur following rash healing.

Herpes and Multiple Sclerosis

[0024] A strain of reactivated herpes virus may be associated withmultiple sclerosis (MS), an autoimmune disorder in which the bodyattacks its own tissues. Results of a study conducted by scientists atthe National Institute of Neurological Disorders and Stroke (NINDS) inBethesda, Md., add to mounting evidence of the role of viral triggers inMS and may serve as the cornerstone for clinical trials usingantiherpetic agents as a treatment. This is the first publishedlarge-scale study suggesting an association of a human herpes virus inthe disease process of MS. In the study, more than 70 percent ofpatients with the relapsing-remitting form of MS showed an increasedimmune response to human herpes virus-6 (HHV-6) and approximately 35percent of all MS patients studied had detectable levels of active HHV-6in their serum. Scientists believe that there may be a point in timeduring the progression of MS when the virus, which lies dormant in thebody for years, reactivates, accounting for its presence in a subset ofMS patients. The study appears in the December 1997 issue of NatureMedicine.

[0025] As many as 350,000 Americans are affected by MS, which is mostoften diagnosed in patients between the ages of 20 and 40 and ischaracterized by muscle weakness, visual disturbances, and a variety ofother neurological impairments. The array and severity of symptomsvaries widely from patient to patient and women are more likely to beaffected than men. The most common form of MS is the relapsing-remittingtype. In this type of MS, new symptoms appear or existing ones becomemore severe, followed by periods of partial or total recovery. Theseflare-ups of new or intensified symptoms last for variable amounts oftime. A second form of MS is a chronic and progressive one in whichsymptoms steadily worsen. HHV-6 is relatively new to scientists and isknown to cause a common childhood illness, roseola. HHV-6 is known to bepresent in 90 percent of the adult American population as a result ofinfection during the first few years of life. Scientists believe thatthe reactivation of HHV-6 virus may be associated with the breakdown ofthe protective covering of nerves, called myelin. Reactivation ischaracteristic of herpes viruses. In the study, investigators screenedthe serum of 102 individuals, 36 of whom had MS. Of the 22 individualswith the relapsing-remitting form of MS, 73 percent had an increase inimmune response to an early antigen of HHV-6, compared to only 18percent of those participants who served as normal volunteers. Inaddition, the scientists detected HHV-6 DNA in the serum (a marker ofactive virus infection) of 15 of 50 individuals with MS. All 47individuals without MS tested negative for the presence of active HHV-6viral infection.

Human Papillomavirus

[0026] Human papillomavirus (HPV) is one of the most common sexuallytransmitted diseases. Genital HPV infections are widespread amongsexually active adults. It is estimated that as many as 40 millionAmericans are infected with HPV, and the incidence of the diseaseappears to be increasing. More than 1000 types of HPV have beenidentified. Some cause common skin warts. Others are spread throughsexual contact and result in genital warts.

[0027] HPV often results in an infection without any visible symptoms.Thus, individuals may not be aware of the infection or of the potentialrisk of transmission to others. Genital warts are spread by sexualcontact and are highly contagious. Approximately two-thirds of peoplewho have sexual contact with a partner with genital warts will developwarts, usually within about three months of contact.

[0028] In women, the warts occur on the outside and inside of thevagina, on the cervix, and around the anus. In men, the warts occur onthe penis, scrotum, and around the anus. Genital warts often occur inclusters, and can be very tiny or can occur in large masses. Treatmentincludes the application of trichloracetic acid or podophyllin solution.Warts can be removed by cryosurgery, electrocautery or surgery. Althoughelimination of the warts is possible, the viral infection persists andwarts often reappear after treatment.

[0029] To date, there are very few satisfactory treatments, vaccines, orcures for viral infection. Drug treatments, either topical or ingested,have shown generally limited benefits. As an alternative to thepharmaceutical approach, the electrical stimulation of infected tissueshas been explored. These methods involve the application of electrodesto the skin near the infected region. Some examples are provided by U.S.Pat. No. 4,913,148 to Diethelm, U.S. Pat. No. 5,133,352 to Lathrop, etal., and U.S. Pat. No. 5,607,461 to Lathrop. The disclosures of each ofthese patents is hereby incorporated by reference in their entireties.Although this technique shows promise, to date, the devices andstimulation protocols used have been less successful at eliminatingviral infection than was hoped.

SUMMARY OF THE INVENTION

[0030] The invention includes methods of treating viral infections. Inone embodiment, such a method comprises a treatment protocol includingthe application of a series of pulses of electrical stimulation to apatient's skin or mucosa, wherein the pulses of electrical stimulationhave varying characteristics over the course of the treatment protocol.The pulses may differ in amplitude or frequency. They may alternatebetween AC pulses and DC pulses.

[0031] Apparatus for applying electrical stimulation to treatphysiological and pathological conditions such as viral infections isalso provided. In one embodiment, the apparatus comprises at least twoelectrodes and a circuit configured to supply both AC and DC voltage tothe electrodes. Other apparatus embodiments include counters fordisplaying the number of treatments applied. Still other embodimentsinclude replaceable and disposable cartridges comprising electrodes anda battery. The battery may be rechargeable with an external charger. Awide variety of rechargeable/disposable batteries are commerciallyavailable with different form factors, costs, etc.

[0032] Advantageous electrode designs for the apparatus are alsoprovided. In one embodiment, the electrode comprise an elongated surfacefor application to the subject's skin or mucosa.

BRIEF DESCRIPTION OF THE DRAWINGS

[0033]FIG. 1A is a perspective view of one embodiment of an electricalstimulation device.

[0034]FIG. 2 is a block diagram of an electrical circuit which isprovided in some advantageous embodiments of the stimulation devices ofthe present invention.

[0035]FIG. 3 is a perspective view of another embodiment of anelectrical stimulation device.

[0036]FIG. 4 is a perspective view of another embodiment of anelectrical stimulation device.

[0037]FIGS. 5A and 5B are side views of another embodiment of theelectrical stimulation device, showing the disposable activator insertedinto, and removed from, the housing.

[0038]FIG. 5C is an end view of the distal end of the device of FIGS. 5Aand 5B, showing the position of the electrodes.

[0039]FIGS. 6A and 6B are side views of yet another embodiment of theelectrical stimulation device, showing the disposable activator insertedinto, and removed from, the housing.

[0040]FIG. 6C is an end view of the distal end of the device of FIGS. 6Aand 6B, showing the position of the electrodes.

[0041]FIG. 7 is a flow chart of an electrical stimulation treatmentprotocol in accordance with one embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0042] Embodiments of the invention will now be described with referenceto the accompanying Figures, wherein like numerals refer to likeelements throughout. The terminology used in the description presentedherein is not intended to be interpreted in any limited or restrictivemanner, simply because it is being utilized in conjunction with adetailed description of certain specific embodiments of the invention.Furthermore, embodiments of the invention may include several novelfeatures, no single one of which is solely responsible for its desirableattributes or which is essential to practicing the inventions hereindescribed.

[0043] Referring now to FIG. 1, there is shown one embodiment of theelectrical stimulation device of the present invention, useful fortreating viral infections. The device 10 includes a housing 12, which isdesigned to fit comfortably in the hand of the user. At one end, twoelectrodes 18 a and 18 b are mounted. The electrodes 18 a, 18 b, have anelongated surface for application to the user's skin. The elongatedelectrodes allow for larger electrode to skin surface contact. As shownin FIG. 1, each electrode 18 a, 18 b may comprise a closed contour. Insome embodiments, the electrodes 18 a, 18 b are concentric closedcontours. In the embodiment of FIG. 1, the electrodes comprise circuittraces plated onto a printed circuit board 19 that is attached to oneend of the housing 12.

[0044] It will be appreciated that the electrodes may take many formsand shapes. The electrodes 18 a and 18 b can be oval or elliptical asshown in FIG. 1, rectangular as shown in FIG. 3, or circular, as shownFIG. 4. They may also be square, or any other desired shape, and arepreferably gold plated. However, any electrically conductive materialcan be used. An on/off button or switch 20 that is manually operated islocated on the device, which also can include a first LED 22 that isactivated when the device is turned on, and a second LED 23 thatindicates a low battery condition. An alphanumeric display 25 may alsobe provided on the device to provide the user with a variety ofinformation concerning device and/or treatment status.

[0045] In operation, the electrodes 18 a and 18 b are placed in contactwith the patient's skin or mucosa, and electrical energy is delivered tothe electrodes 18 a and 18 b when the device is turned on. As will bedescribed in additional detail below, the treatment protocol typicallyinvolves the application of a series of electrical pulses to theaffected area. In this embodiment, the display 25 may show exhibit acount of the number of treatments applied, thus indicating to the userat any given time how much of the treatment protocol has been completed.

[0046]FIG. 2 illustrates the circuitry provided inside the housing 12 ofsome advantageous embodiments of the invention. The device willgenerally include a battery 16, which may be rechargeable or disposable,coupled to a logic/processor circuit 14, a signal generator circuit 17,and the display 25. The logic/processor circuit 14 drives the display 25and configures the signal generator circuit 17 to output the desiredelectrical signal to the electrodes 18 a and 18 b. Although shown asseparate blocks in FIG. 2, it will be appreciated that thelogic/processor circuit 14 and the signal generator circuit 17 may befunctionally combined, and will typically reside on a common printedcircuit board in the housing 12. The types of signals produced by thesignal generator circuit 17 in advantageous embodiments of the inventionwill be described in additional detail below.

[0047] The physical size and shape of the device will advantageouslyvary depending on the specific intended application. The embodimentillustrated in FIG. 1, for example, is advantageously sized for use onthe legs and genital area. In this embodiment, the electricalstimulation device 10 is approximately 2-3 inches long, approximately1-1.5 inches wide, and approximately 0.5-1 inches deep. As noted above,the device 10 is sized so as to fit comfortably in the hand of the user.The circuit traces forming the concentric electrodes 18 a, 18 b shown inFIG. 1 are approximately 2-3 mm in width, and are plated to a thicknessof less than 1 mm. As illustrated in FIG. 3, in an alternativeembodiment of the genital appplicator, the end of the device 10 whichmounts the electrodes is curved so that it is easier to produce contactbetween the skin of the patient and the entire electrode surface.

[0048] Turning now to FIG. 4, there is illustrated another embodiment ofthe electrical stimulation device 10. The device 10 includes a housing12 and concentric electrodes 18 a and 18 b at the top end of the device10. Here, the electrodes 18 a and 18 b are circular, and the centerelectrode 18 b forms a circular pad rather than a ring. This embodimentis adapted for oral application, and advantageously measures about 0.5to 0.75 inches in diameter with a length of about 2 inches. This isabout the same size and shape of a lipstick or lip balm applicator, andthus is very convenient for carrying in a pocket or purse. In thisembodiment, the display 25 may be provided on the bottom flat surfaceopposite the electrode surface. A cap 22 is also preferably provided forthe embodiments of FIGS. 1, 3, and 4. This cap 22 fits over the top endof the device 10 where the electrodes 18 a and 18 b are located. The cap22 acts to protect the electrodes 18 a and 18 b after cleaning withalcohol or hydrogen peroxide and not in use.

[0049] In FIGS. 5A, 5B, 6A and 6B there is shown still other embodimentsof the electrical stimulation device 10 of the present invention. Inthese embodiments, The device 10 includes a disposable electrodecartridge 24 which includes the battery and concentric electrodes 18 aand 18 b located on the contact head 26 of the device 10, which islocated at the distal end 30 of the device 10. The contact head 26 canbe flat (FIGS. 5A and 5B) or hemispherical in shape (FIGS. 6A and 6B).The disposable electrode cartridge 24 snaps into the housing 12, but canbe easily removed for disposal. As shown in FIG. 5C, the concentricelectrodes 18 a, 18 b, can be circular; alternatively, as shown in FIG.6C, the electrodes 18 a, 18 b can be positioned side-by-side, eachelectrode comprising approximately half of a hemispherical surface,separated by a strip of insulating material 26 along an equatorial lineof the hemisphere. This embodiment is advantageous in that theelectrodes can be removed and replaced without discarding the entireunit 10.

[0050] The devices described above are used by applying the electrodesto the surface of the affected skin or mucosa and delivering electricalenergy to the affected area. It has been found advantageous for a totaltreatment protocol to comprise a series of electrical pulses, withdifferent pulses being different in signal characteristics. The pulsesmay differ in one or more of amplitude, frequency, signal type, e.g. ACor DC or any other electrical signal characteristic. It is hypothesizedthat the different electrical signal characteristics produce differentdisruptive effects on the virus, thus preventing the survival of thoseviruses which may already be or which may become resistant to any oneform of electrical stimulation

[0051] This form of treatment protocol is illustrated in FIG. 7, and isinitiated at start block 30. At block 32, an electrical signal pulse isapplied. At decision block 34, it is determined whether or not the pulsejust applied is the last pulse of the treatment. If not, the systemmoves to block 36, where the device is configured to output a pulsehaving characteristics different from the previous pulse. Looping backto block 32, the pulse having the new desired characteristics isapplied. This process continues until the last pulse of the treatment isapplied, and the treatment then ends at stop block 38.

[0052] As mentioned above, the pulses may differ in any one or more of avariety of characteristics. The pulses may change in maximum voltage orcurrent amplitude. The pulses may change between AC waveforms and DCwaveforms. AC pulses may vary in frequency or waveform such as trianglewaves, square waves, or sine waves. As described below, in someadvantageous embodiments, the pulses vary in maximum amplitude fromapproximately 3 volts to approximately 20 volts, and vary in frequencyfrom DC to about 10 kHz.

[0053] Two different specific protocols based on the principlesdescribed above have been devised. Protocol 1 involves ten 30 secondapplications of electrical energy, with a one hour break between eachone, wherein each 30 second segment is itself divided into sub-segments,which in this embodiment may be 5, 1, and/or 0.2 second intervals. Thistreatment protocol is defined as follows:

[0054] If the ten applications are designated numbers 1 through 10,applications 1, 3, 5, 7, and 9 are as follows: TABLE 1 5 seconds at 9VDC 1 second each at 5, 10, 25, 50, and 75 Hz, at 9 VAC peak. 5 secondsat 9 VDC 1 second each at 100, 200, 300, 400, and 500 Hz, at 9 VAC peak.5 seconds at 9 VDC 1 second each at 500, 300, 100, 50, and 5 Hz, at 9VAC peak.

[0055] Applications 2, 4, 6, 8 and 10 are as follows, all at 9 VAC peak:TABLE 2 25 step frequency sweep from 5 Hz to 1000 Hz, 0.2 seconds ateach frequency, 9 VAC 25 step frequency sweep from 1000 Hz to 5 Hz, 0.2seconds at each frequency 25 step frequency sweep from 5 Hz to 1000 Hz,0.2 seconds at each frequency 25 step frequency sweep from 1000 Hz to 5Hz, 0.2 seconds at each frequency 25 step frequency sweep from 5 Hz to1000 Hz, 0.2 seconds at each frequency 25 step frequency sweep from 1000Hz to 5 Hz, 0.2 seconds at each frequency

[0056] In the above described protocol, the peak voltage remainsconstant at about 9 V. A more complex protocol, referred to herein asProtocol 2, has also been developed which includes variation in peakvoltage as well as variations in waveform and frequency. In thisspecific protocol, nineteen different pulses that have been found usefuland are set forth below in Tables 3 and 4. Twelve of the pulses are ACwaveforms, and seven of the pulses are DC waveforms. Table 5 sets forth10 different pulse sequences which are applied in various combinationsto the affected area during a treatment protocol. TABLE 3 1st 2nd 3rd4th 5th 6th 7th 8th 9th second second second second second second secondsecond second A1 5 Hz 10 Hz 25 Hz 50 Hz 75 Hz A2 25 step sweep from 5 Hzto 1 kHz A3 1 kHz  2 kHz  3 kHz  4 kHz  5 kHz A4 25 step sweep from 1kHz to 5 Hz A5 5 Hz 10 Hz 25 Hz 50 Hz 75 Hz 100 Hz A6 1 kHz  2 kHz  3kHz  4 kHz  5 kHz  7 kHz A7 5 Hz 10 Hz 25 Hz 50 Hz 75 Hz 100 Hz 125 HzA8 1 kHz  2 kHz  3 kHz  4 kHz  5 kHz  7 kHz  9 kHz A9 25 step sweep from10 Hz to 2.5 kHz A10 25 step sweep from 2.5 kHz to 10 Hz A11 5 Hz 10 Hz25 Hz 50 Hz 75 Hz 100 Hz 125 Hz 150 Hz 200 Hz A12 1 kHz  2 kHz  3 kHz  4kHz  5 kHz  7 kHz  9 kHz  10 kHz

[0057] TABLE 4 1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th 11th secondsecond second second second second second second second second second D13 V 4 V 5 V 7 V 9 V D2 3 V 4 V 5 V 7 V 9 V 11 V D3 3 V 4 V 5 V 7 V 9 V11 V 13 V D4 3 V 4 V 5 V 7 V 9 V 11 V 13 V 15 V D5 3 V 4 V 5 V 7 V 9 V11 V 13 V 15 V 17 V D6 3 V 4 V 5 V 7 V 9 V 11 V 13 V 15 V 17 V 19 V D7 3V 4 V 5 V 7 V 9 V 11 V 13 V 15 V 17 V 19 V 20 V

[0058] TABLE 5 PULSE SEQUENCE 1 A1 D1 A2 D1 A3 D1 A4 2 A1 D1 A2 D1 A3 D1A4 A1 3 A1 D1 A2 D1 A3 D1 A4 D1 A1 4 A1 D1 A2 D1 A3 D1 A4 D1 A1 D1 5 A1D2 A2 D2 A3 D2 A4 D2 A1 D2 A2 6 A1 D3 A2 D3 A3 D3 A4 D3 A1 D3 A2 D3 7 A1D4 A2 D4 A3 D4 A4 D4 A1 D4 A2 D4 A3 8 A5 D5 A9 D5 A6 D5 A10 D5 A5 D5 A9D5 A6 D5 9 A7 D6 A9 D6 A8 D6 A10 D6 A7 D6 A9 D6 A8 D6 A10 10 A11 D7 A9D7 A12 D7 A10 D7 A11 D7 A9 D7 A12 D7 A10

[0059] Treatment 1

[0060] Sequence 1 at 3V

[0061] hour break

[0062] Sequence 1 at 5V

[0063] hour break

[0064] Sequence 1 at 7V

[0065] hour break

[0066] Sequence 1 at 9V

[0067] hour break

[0068] Sequence 1 at 11V

[0069] Treatment 2

[0070] Sequence 1 through 10 at 3V

[0071] hour break

[0072] Sequence 1 through 10 at 5V

[0073] hour break

[0074] Sequence 1 through 10 at 7V

[0075] hour break

[0076] Sequence 1 through 10 at 9V

[0077] hour break

[0078] Sequence 1 through 10 at 11V

[0079] Treatment 3

[0080] Sequence 1 through 10 at 3V

[0081] hour break

[0082] Sequence 1 through 10 at 5V

[0083] hour break

[0084] Sequence 1 through 10 at 7V

[0085] hour break

[0086] Sequence 1 through 10 at 9V

[0087] hour break

[0088] Sequence 1 through 10 at 11V

[0089] hour break

[0090] Sequence 1 through 10 at 13V

[0091] hour break

[0092] Sequence 1 through 10 at 15V

[0093] hour break

[0094] Sequence 1 through 10 at 17V

[0095] hour break

[0096] Sequence 1 through 10 at 19V

[0097] hour break

[0098] Sequence 1 through 10 at 20V

[0099] Treatment 4

[0100] Sequence 1, 3V

[0101] Sequence 2, 5V

[0102] Sequence 3, 7V

[0103] Sequence 4, 9V

[0104] Sequence 5, 11V

[0105] Sequence 6, 13V

[0106] Sequence 7, 15V

[0107] Sequence 8, 17V

[0108] Sequence 9, 19V

[0109] Sequence 10, 20V

[0110] Repeat 10 times with one hour break between each repetition.

[0111] In these treatment sequences, the peak AC and DC voltages arespecified. Thus, in the case of the application of a DC pulse, themaximum voltage applied will be limited by either the maximum specifiedin Table 4, or by the maximum specified by the particular treatmentsegment being applied. Thus, If D7 is being applied at 7 V, the pulseapplied is one second at 3V, one second at 4V, one second at 5V, andeight seconds at 7V. However, if D7 is being applied at 20V, the pulseapplied is one second each at 3V, 4V, 5V, 7V, 9V, 11V, 13V, 15V, 17V,19V, and 20V. If D1 is applied at 20 V, the pulse is one second at 3V,one second at 4V, one second at 5V, one second at 7V, and one second at9V. All AC pulses have peak voltages as specified by the treatmentsegment being applied.

[0112] Treatment should be begun as soon as possible after the onset ofsymptoms, preferably in the prodromal stage when the characteristictingling, itching or burning sensation is felt. The distal end of thedevice is held to the affected skin or mucosa where symptoms areperceived, and treatment is commenced by pressing the “on” button. Adesignated treatment cycle of about 30 to 60 seconds is automaticallyinitiated. The LED illuminates during this on cycle.

[0113] The user generally will not feel any sensation during treatment.By the end of the 10×30 second consecutive treatments of Protocol 1, orby the end of Treatment 1 of Protocol 2, prodromal symptoms shouldcease. If symptoms continue, or if lesions occur or are still present,it is recommended that treatment be continued. Under protocol 1, thiswould involve a second course of 10 consecutive 30 second treatments.Under Protocol 2, Treatment 2 as defined above should be administered.If, after this second course of treatments, symptoms or lesions appearor persist, a third course of ten treatments should be carried out underProtocol 1, or Treatment 3 of Protocol 2 should be applied. Finally, ifsymptoms still remain, Protocol 2 calls for the application of Treatment4 as defined above.

[0114] It will be appreciated that a wide variety of treatment protocolscould be devised based on the principles of the invention, and that thetwo described above are only two specific examples of treatmentprotocols with the advantageous feature of pulse variability.

[0115] A number of device electrode placement protocols can be employedwith the present invention and these involve various anatomical sites.Electrode placement sites may be in relationship to neural ganglia whereviruses establish residence. For example, the trigeminal ganglion nearthe ear is a site where HSV-1 (herpes labialis) establishes residence,from which it recurs on the lower lip or face. Therefore this site isideal for electrode placement and is located in front of the ear(external auditory meatus), below the zygomatic arch, and over theposition of the facial nerve and parotid gland. Another neural ganglionexample for electrode placement is the sacral ganglion at the base ofthe spine. This is where HSV-2 (genital herpes) sets up residence fromwhich it recurs in the genital area.

[0116] Other electrode placement sites can be in relationship toregional lymph nodes. Examples of these sites would be in the cervicalchain of lymph nodes positioned bilaterally at the front of the neck,lymph nodes in the tonsil bed positioned just under the angle of the jaw(junction of horizontal and ascending ramus of mandible), in theaxillary chain of lymph nodes positioned under the arms, and in theinguinal lymph nodes positioned bilaterally in the groin.

[0117] Further sites for electrode placement can be in relationship toair sinuses such as those in the facial bones of the skull. Examplesinclude the maxillary antrum positioned below the eyes and above theupper teeth, accessed by placement either side of the nose level withthe eyes, and the frontal sinus positioned either side of the midline onthe forehead just above the eyes.

[0118] With the treatment of viral diseases that affect the whole body,and for serious and life threatening viral diseases such as HIV andAIDS, it will be necessary to carry out treatments using placements ofthe electrical device in other additional anatomical regions using aconsecutive pattern of treatments.

[0119] In one such protocol, the device is used consecutively on threedifferent anatomical regions of the body. These three sites are referredto collectively as “The Central Location.” In this, the first placementsite is in the center of the spine, slightly above the level of theshoulders, which is the position of cervical vertebra #7, referred to asC7. The second site is also positioned longitudinally in the center ofthe spine but between the neck and the base of the spine, which is atabout thoracic vertebra #7 (T7). The third and last position is also inthe center of the spine but positioned at the base of the lumbar spineequivalent with the 5th lumbar vertebra, referred to as L5.

[0120] In another protocol, a further seven anatomical placement sitesare employed in addition to the above three sites of The CentralLocation. Whereas the three previous sites are on the back, or dorsalposition, of the body, the seven additional sites are located on thefront, or ventral position, of the body. These seven differentanatomical regions of the body coincide with the seven “chakras” andchannels of energy. Many workers have contemplated that in addition to anetwork of nerves and sensory organs, there also exists a subtle systemof channels and centers of energy (chakras) which affects the physical,intellectual, emotional and spiritual being. These seven regions areused as electrode placement sites and are positioned in seven specificregions of the body ranging from the crown to the sternum, includingregions such as the heart. The seven regions are generally referred toas the crown, root, sacral, solar plexus, heart, throat, and third eyechakras. These seven locations physically correspond to the locations ofthe top of the head, between the anus and the genitals, between thenavel and the genitals, between the navel and the base of the sternum,in the center of the chest, centrally at the base of the throat, andabove and between the eyebrows respectively.

[0121] In these two final protocol examples of treating viral infectionsof the entire body, the treatment sequences shown in Table 5, and inTreatment 4, are employed whereby ten different pulse sequences areapplied in various combinations. Each of the ten separate outputs rampup consecutively through the various voltage levels resulting in a totaltreatment time of eight minutes and forty-five seconds in eachanatomical site. This regimen may be carried out on each of either thethree regions in The Central Location or, additionally, the seven chakraregions as described above, making ten anatomical sites in all.

[0122] The three Central Location sites would give a total treatmenttime of 3×8 minutes and 45 seconds, which is 26 minutes and 15 seconds.The seven chakra regions would give a total treatment time of sixty-oneminutes and fifteen seconds. Treatment of all ten locations would give atotal treatment time of 87 minutes and thirty seconds. The entiresequence would then be repeated according to the protocol employed whichcould be, for example, nine repetitions, which is ten treatments in all.

[0123] Use of a stimulation device in the treatment of various forms ofviral infections are further described in the following specificexamples.

EXAMPLE 1 Oral Herpes

[0124] A female subject, date of birth Mar. 15, 1975, had a twelve yearhistory of oral herpes infections. Outbreaks tended to occur at the lipborders, especially the lower lip, and were more frequent during coldweather and during times of stress. She reported approximately four tosix outbreaks per year, each lasting about 10-12 days. Previoustreatments had been unsuccessful.

[0125] The subject was given an electrical stimulation device asdescribed above that was configured to apply Protocol 1 as describedabove. She was instructed to apply the device directly to the infectedarea or areas, and apply the ten 30 second treatments as described inProtocol 1 above, with a one hour break between each 30 secondtreatment. The device was configured to automatically step through theten different electrical pules as shown above as the subject applied thedevice for the ten consecutive 30 second periods. Thus, the subject onlyhad to place the electrodes on the affected area, press the ON button,and wait for an LED display to turn off after 30 seconds.

[0126] After the first treatment, the subject reported that the smallveiscles that had begun to develop started to dry up immediately aftertreatment. The small reddish areas indicating the onset of an outbreakdisappeared completely within three days, as did any symptoms of burningor itching.

EXAMPLE 2 Recurrent Genital Herpes

[0127] The male subject, date of birth Dec. 25, 1955, had a history ofgenital herpes for the past 20 years. The outbreaks always occurred onhis penis and varied from minor outbreaks to major ones. The subjectreported that he had four outbreaks on average each year. He alsoreported that in his opinion, they often occurred in relation to stressand when he was working very hard physically.

[0128] The subject had an outbreak which was preceded by prodromesymptoms. The subject reported that his thighs began to tingle and feel“funny”, which is what usually happened just before an outbreak. The dayfollowing the prodrome symptoms, the subject noticed a small raised redlump on the top of the head of his penis. The subject started treatmentwith the device of the present invention on the red spot once every hourfor a total of ten treatments using Protocol 1 as described above and asin Example 1. The subject reported that the red spot did not get anylarger like it usually did, and was not painful, also a typical since itusually was very painful by the second day. The subject reported thatthe red spot did not progress to the blister stage. This was the firsttime in his twenty-year history of having genital herpes that anoutbreak did not progress to a blister stage. The subject also reportedthat there was no release of fluid which was also unusual. The outbreakdried up and disappeared completely after the third day.

[0129] The subject had another prodrome stage where the symptoms weresimilar to those described previously; his thighs started to tingle andburn. The subject noticed that a small outbreak had developed on theunderside of his penis and appeared as a raised red spot. This becamelarger and the subject reported that this had all of the signs of beingone of his major outbreaks that he got regularly about once a year. Thesubject started using the device for treatment as soon as he noticed theoutbreak. He used the device every hour as instructed, positioning thetip of the device on the red raised lesion, in the same manner asdescribed above. The lesion did not get any larger once treatmentstarted. The subject reported that after the appearance of the red spotand commencement of treatment, there was no formation of blisters, nowetness or oozing of fluid, and no pain. The subject reported that theoutbreak started to resolve itself the day after commencing treatmentwith the device.

[0130] Seven months later, the subject reported that he noticed a littlered colored spot appear on the upper side of his penis which swelled anddeveloped into a small bump. The subject reported that there were nosigns of a prodrome stage this time. He used the viral device with thesame treatment regimen of once an hour, and during treatments, the smallbump did not get any larger, and disappeared after a couple of days. Thesubject reported that this was the “best” outbreak he had in the lasttwenty years because there was no pain, no swelling, and no discharge,and it was all over in a couple of days.

[0131] Three months later, the subject reported that he had a very smalloutbreak on the left rear thigh. It appeared as a small red spot butthere was no evidence of any lesion on his penis. He used the viraldevice on top of the lesion employing the same protocol as describedabove, and the small lesion did not get any bigger. The subject reportedthat there was no blistering, no discharge and no pain. The outbreakcleared up completely in a couple of days.

[0132] Five months later, the subject reported the appearance of a smallred swelling on the side of his penis. As soon as he saw evidence of theoutbreak he started treatment with the device using the once-an-hourprotocol described above. The lesion did not progress in size, did notblister, and was not painful. It responded well to the treatment and thelesion disappeared by day three.

EXAMPLE 3 Human Papiloma Virus

[0133] A female subject, date of birth Jun. 21, 1951, had a history oflesions appearing on the lower part of her legs, generally on the frontaspect between the knee and the ankle. An outbreak usually consisted of2-3 to six or more lesions, and tended to occur during times of stress.The lesions would become larger over a period of five to seven days, andwould dry up and disappear two to three weeks after their appearance.The lesions were diagnosed as being caused by Human Papiloma Virus, forwhich oral medication and topical cream was prescribed. These treatmentswere not successful.

[0134] The subject then tried the electrical stimulation device of thepresent invention, using it directly on the lesions for ten 30 secondtreatments as described above in Examples 1 and 2. She treated eachlesion separately, unless two were very close together, in which casethe electrodes were placed between the two lesions.

[0135] The subject reported that the pain subsided immediately, and thatthe lesions healed and disappeared within three days.

EXAMPLE 4 Verruca

[0136] A male subject, date of birth May 28, 1949, developed a verrucawart on the sole of his right foot. The lesion was positioned at thefront and in the center of the planter surface of the foot immediatelyto the side of the large toe prominence. It interfered with thesubject's walking and running. The subject had tried a number oftreatments, including 40% salicylic acid pads, but these did noteliminate the wart or the associated pain and discomfort.

[0137] The subject used the stimulation device described above for ten30 second treatments as in Examples 1-3. After the ten treatments, thesubject reported that the pain had stopped completely. The lesion wasstill visible as a raised area on the planter surface of the foot, and asecond series of ten treatments was applied, commencing about one hourafter the conclusion of the first series of ten treatments. By the endof the second course of treatment, the lesion appeared different intexture, was less swollen, and was not painful. The subject was advisedto foot file the region, which he did, after which the affected arealooked normal.

[0138] Follow up with the subject over nine months following treatmentrevealed that he was completely pain free, with no evidence that theverruca had returned.

[0139] Thus, the method and device described herein were found to beeffective in the treatment of viral infection. The treatment with thedevice not only improved recovery time, but also reduced the frequencyof recurrence.

[0140] The foregoing description details certain embodiments of theinvention. It will be appreciated, however, that no matter how detailedthe foregoing appears in text, the invention can be practiced in manyways. As is also stated above, it should be noted that the use ofparticular terminology when describing certain features or aspects ofthe invention should not be taken to imply that the terminology is beingre-defined herein to be restricted to including any specificcharacteristics of the features or aspects of the invention with whichthat terminology is associated. The scope of the invention shouldtherefore be construed in accordance with the appended claims and anyequivalents thereof.

What is claimed is:
 1. A method of treating viral infections comprisingapplying electrical stimulation to the skin or mucosa of a patient,wherein said electrical stimulation is applied as a series of electricalpulses, wherein different pulses in said series have different maximumamplitudes.
 2. The method of claim 1, wherein said pulses progressivelyincrease or decrease in maximum voltage or current amplitude
 3. Themethod of claim 1, wherein said pulses progressively increase in maximumvoltage or current amplitude.
 4. The method of claim 1, wherein some ofsaid series of pulses comprise AC waveforms, and wherein some of saidseries of pulses comprise DC waveforms.
 5. The method of claim 4,wherein at least a portion of said series of pulses alternates betweenAC and DC pulses.
 6. The method of claim 1, wherein said pulses vary inmaximum amplitude from approximately 3 volts to approximately 20 volts.7. A method of treating viral infections comprising applying electricalstimulation to the skin or mucous membranes of a patient, wherein saidelectrical stimulation is applied as a series of electrical pulses,wherein different pulses in said series have different frequencies. 8.The method of claim 7, wherein said pulses have different maximumamplitudes.
 9. A method of treating viral infections comprising theapplication of alternating periods of AC and DC electrical stimulation.10. The method of claim 9, wherein said alternating periods of AC and DCelectrical stimulation progressively increase in amplitude.
 11. Themethod of claim 9, wherein different periods of AC stimulation havedifferent frequencies.
 12. The method of claim 9, wherein saidfrequencies progressively increase or decrease in frequency within oneof said AC periods.
 13. An apparatus for treating viral infections withelectrical stimulation comprising: at least two electrodes; and acircuit configured to supply both AC and DC voltage to said electrodesat voltages of less than or equal to about 20 volts.
 14. An apparatusfor treating viral infections with electrical stimulation comprisingfirst and second electrodes, wherein said first and said secondelectrode each comprise an elongated surface for application to apatient's skin or mucosa.
 15. The apparatus of claim 14, wherein saidelongated surface of said first electrode comprises a firstsubstantially closed contour, and wherein said elongated shaped surfaceof said second electrode comprises a second substantially closedcontour.
 16. The apparatus of claim 15, wherein said secondsubstantially closed contour surrounds said first closed contour. 17.The apparatus of claim 16, wherein said first and said second closedcontours comprise concentric circular contours.
 18. The apparatus ofclaim 16, wherein said first and said second closed contours compriseconcentric rectangular contours.
 19. The apparatus of claim 16, whereinsaid first and said second closed contours comprise concentric squarecontours.
 20. The apparatus of claim 16, wherein said first contourcomprises an approximately semi-circular contour having first and secondends, wherein said second contour comprises an approximatelysemi-circular contour having first and second ends, wherein said firstend of said first contour is adjacent to said first end of said secondcontour, and wherein said second end of said first contour is adjacentto said second end of said second contour.
 21. An apparatus for applyingelectrical stimulation to a patient's skin or mucous membranes fortreating viral infections comprising a surface for contact with saidpatient's skin, said surface being approximately hemispherical in shapeand comprising a pair of electrodes.
 22. A device for treating viralinfections comprising: a housing; an electrical signal source mounted tosaid housing; one or more electrodes for application to a patient's skinor mucous membranes, wherein said electrodes are coupled to saidelectrical signal source so as to be energized by said electrical signalsource; a counter mounted to said housing, wherein said counter isconfigured to display a count of the number of times said electricalsignal source has energized said electrodes.
 23. The device of claim 26,wherein said counter comprises a multi-segment LCD display.
 24. A methodof treating viral infections comprising: applying current flow in afirst direction through tissue infected with virus; and applying currentflow in a second direction opposite said first direction through saidtissue.
 25. The method of claim 30 comprising applying a variablefrequency bipolar waveform.
 26. A method of treating viral infectionscomprising a treatment protocol including the application of a series ofpulses of electrical stimulation to a patient's skin or mucosa, whereinsaid pulses of electrical stimulation have varying characteristics overthe course of said treatment protocol.
 27. The method of claim 32wherein said viral infection comprises a herpes virus infection.
 28. Themethod of claim 32 wherein said viral infection comprises a humanpapiloma virus infection.